title: Stem cells as a good tool to investigate dysregulated biological systems in autism spectrum disorders.
abstract: Identification of the causes of autism spectrum disorders (ASDs) is hampered by their genetic heterogeneity; however, the different genetic alterations leading to ASD seem to be implicated in the disturbance of common molecular pathways or biological processes. In this scenario, the search for differentially expressed genes (DEGs) between ASD patients and controls is a good alternative to identify the molecular etiology of such disorders. Here, we employed genome-wide expression analysis to compare the transcriptome of stem cells of human exfoliated deciduous teeth (SHEDs) of idiopathic autistic patients (n = 7) and control samples (n = 6). Nearly half of the 683 identified DEGs are expressed in the brain (P = 0.003), and a significant number of them are involved in mechanisms previously associated with ASD such as protein synthesis, cytoskeleton regulation, cellular adhesion and alternative splicing, which validate the use of SHEDs to disentangle the causes of autism. Autistic patients also presented overexpression of genes regulated by androgen receptor (AR), and AR itself, which in turn interacts with CHD8 (chromodomain helicase DNA binding protein 8), a gene recently shown to be associated with the cause of autism and found to be upregulated in some patients tested here. These data provide a rationale for the mechanisms through which CHD8 leads to these diseases. In summary, our results suggest that ASD share deregulated pathways and revealed that SHEDs represent an alternative cell source to be used in the understanding of the biological mechanisms involved in the etiology of ASD.
authors.affiliation: Centro de Estudos do Genoma Humano, Departamento de Biologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Karina
authors.initials: K
authors.lastname: Griesi-Oliveira
authors.forename: Daniele Yumi
authors.initials: DY
authors.lastname: Sunaga
authors.forename: Lucas
authors.initials: L
authors.lastname: Alvizi
authors.forename: Estevão
authors.initials: E
authors.lastname: Vadasz
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Passos-Bueno
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D003599:Cytoskeleton / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003782:Dental Pulp / Q000166:cytology*; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis / Q000235:genetics; D013234:Stem Cells / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*
chemical_list: C523331:CHD8 protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors
keywords: CHD8; androgen signaling; expression studies; stem cells of human exfoliated deciduous teeth